Ultrastructure and chromogranin A immunogold labelling of ECL cell carcinoids

Abstract

Poorly differentiated neuroendocrine cells can be difficult to recognise. Sensitive methods are needed to label cells that have lost their ultrastructural features and have reduced concentrations of neuroendocrine markers. In gastric neoplasms, enterochromaffin-like cells might dedifferentiate and lose their characteristic granules and secretory vesicles, making detection of such cells increasingly difficult. However, chromogranin A (CgA) immunogold labelling could provide sensitive and specific detection of gastric neuroendocrine cells. We present ultrastructural findings, CgA immunogold labelling as well as conventional immunohistochemical findings of two human enterochromaffin-like cell carcinoids. Electron-dense granules of poorly differentiated cells were less intensely labelled than granules in well-differentiated cells. Granules with atypical shape as well as punctuate granules previously found in neuroendocrine neoplasms were also CgA labelled. The CgA labelling efficacy after antigen retrieval in an alkaline solution was higher after heating in an autoclave at 135 degrees C compared to a microwave at 100 degrees C for both granules and secretory vesicles without significant deterioration of the ultrastructure. In conclusion, the use of CgA immunogold labelling could ensure a specific classification of cells with neuroendocrine granules and be a supplement to immunohistochemical examination of poorly differentiated tumours.

The Development and Characterization of a Human Midgut Carcinoid Cell Line

“…The BON cell line was derived from a lymph node metastasis of a highly malignant pancreatic NET and is of foregut origin. Midgut carcinoids, such as the source of our CNDT2 cells, originate from the enterochromaffin-like cells of the intestine, which may vary in their neurosecretory granule production (25). In addition to the presence of these ultrastructural features, on H&E staining, the patient's primary tumor and the CNDT2.1 tumor xenografts showed morphologic characteristics of NETs, such as a round, condensed chromatin pattern (salt-and-pepper nuclei) and an acidic cytoplasm along with an insular growth pattern (8,9).…”

Neuroendocrine Differentiation in Prostate Cancer: From Lab to Bedside

“…Moreover, based on ChrA immunogold labeling techniques, Fossmark et al [17] achieved a good classification of cells with few NE granules and suggested these techniques as an important supplement to standard diagnostic tools in the examination of poorly differentiated tumors, at least in enterochromaffin-like cell carcinoids.…”

Scandinavian journal of gastroenterology – the editors-in-chief

“…Later, he published several hallmark studies on the regulation of gastric acid secretion with the interaction between the principal gastric acid secretagogues and localization of the gastrin receptor, partially through the utilization of the totally isolated, vascularly perfused rat stomach model [72][73][74][75]. He elucidated the role of neuroendocrine cells in carcinogenesis, its possible relation to potent acid inhibitions, and the utility of Chromogranin A as a neuroendocrine marker [76][77][78][79][80]. He developed a rodent model (Japanese cotton rat) to study ECL cell tumourigenesis [78] and later combined physiology, animal models and human studies on for an improved understanding of the development of gastric carcinomas.…”